What is the treatment for Clostridioides difficile (C. diff) infection?

Treatment of Clostridioides difficile Infection

For initial C. difficile infection, oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the first-line treatments, with fidaxomicin preferred when recurrence risk is high; metronidazole should only be used when vancomycin and fidaxomicin are unavailable. 1, 2

Disease Severity Classification

Before initiating treatment, classify disease severity to guide therapy selection:

Non-severe CDI is defined by:

• White blood cell count ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 2
• Stool frequency <4 times daily with no signs of severe colitis 3, 1

Severe CDI is characterized by:

• White blood cell count ≥15,000 cells/mL OR serum creatinine ≥1.5 mg/dL 2
• Additional markers include fever >38.5°C, hemodynamic instability, signs of peritonitis or ileus, elevated serum lactate, pseudomembranous colitis on endoscopy, or colonic wall thickening on imaging 3, 1

Fulminant CDI presents with:

• Hypotension, shock, ileus, or toxic megacolon 2
• Colonic perforation or systemic inflammation with deteriorating clinical condition 3

Initial Episode Treatment Algorithm

Non-Severe Disease

Primary options:

• Oral vancomycin 125 mg four times daily for 10 days 2, 4
• Fidaxomicin 200 mg twice daily for 10 days 2, 4

Alternative (only if vancomycin/fidaxomicin unavailable):

• Metronidazole 500 mg orally three times daily for 10 days 3, 1

Severe Disease

Preferred treatment:

• Oral vancomycin 125 mg four times daily for 10 days 3, 2
• Fidaxomicin 200 mg twice daily for 10 days is also acceptable 2

Critical point: Metronidazole should NOT be used for severe disease due to significantly lower cure rates (76% vs 97% for vancomycin) 2

Fulminant Disease

Combination therapy required:

• High-dose oral vancomycin 500 mg four times daily PLUS 3
• IV metronidazole 500 mg every 8 hours 3, 2
• If ileus present, add intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours via retention enema 3
• Consider vancomycin 500 mg four times daily via nasogastric tube if oral route compromised 3

Critical Management Principles

Immediate actions:

• Discontinue offending antibiotics as soon as clinically feasible; approximately 25% of mild cases resolve with this alone 1, 2
• Avoid antiperistaltic agents and opiates entirely—they worsen colitis and increase complications 3, 1, 2
• Assess clinical response by 72 hours; if no improvement, escalate therapy 2

Supportive care for severe/fulminant disease:

• Aggressive IV fluid resuscitation and electrolyte replacement 3
• Consider albumin supplementation if serum albumin <2 g/dL for both supportive and anti-toxin properties 3
• Monitor intra-abdominal pressure when risk factors for abdominal compartment syndrome present 3

Recurrent CDI Management

Approximately 20-25% of patients experience at least one recurrence 3, 1

First recurrence:

• Oral vancomycin 125 mg four times daily for 14 days OR fidaxomicin 200 mg twice daily for 10 days 3
• Fidaxomicin demonstrates lower recurrence rates after first recurrence 3
• Metronidazole is NOT recommended due to lower sustained response rates and cumulative neurotoxicity risk 3, 2

Second and subsequent recurrences:

• Oral vancomycin 125 mg four times daily for at least 10 days, followed by tapered/pulsed regimen 3, 1
• Example taper: vancomycin 125 mg four times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks 3
• Fecal microbiota transplantation should be offered after multiple recurrences despite appropriate antibiotic therapy 5, 6, 7

Surgical Intervention Criteria

Urgent colectomy indicated for:

• Colonic perforation 3, 1
• Toxic megacolon 3, 1
• Severe ileus 3, 1
• Systemic inflammation with deteriorating clinical condition not responding to antibiotics 3, 1

Timing is critical: Surgery should be performed before serum lactate exceeds 5.0 mmol/L, as mortality increases dramatically with advanced disease 3, 1

Common Pitfalls and Caveats

Antibiotic considerations:

• Fluoroquinolones significantly increase risk of worsening CDI and must be avoided 1
• Metronidazole should never be used for severe disease or for prolonged/repeated courses due to irreversible neurotoxicity risk 2
• Teicoplanin 100 mg twice daily may substitute for oral vancomycin if available 3, 1

Infection control:

• Hand hygiene requires soap and water, NOT alcohol-based sanitizers—alcohol is ineffective against C. difficile spores 1
• During outbreaks, soap and water is mandatory 7

Medication management:

• Discontinue proton pump inhibitors if not medically necessary, as they increase CDI risk 1
• Do NOT perform "test of cure" after completing treatment; only test symptomatic patients 2

Treatment response:

• Treatment response typically requires 3-5 days 2
• If no improvement by day 3-5, do not continue current therapy—escalate immediately 2

Pediatric considerations (6 months to <18 years):

• Dosing based on weight: 4-7 kg receive 80 mg twice daily; 7-9 kg receive 120 mg twice daily; 9-12.5 kg receive 160 mg twice daily; ≥12.5 kg receive 200 mg twice daily 4
• Oral suspension must be refrigerated and discarded after 12 days 4